-
Drugs used to facilitate clotting
-
Fibrinolytic inhibitors
-
MOA: competitively inhibits plasminogen activation
-
Aminocaproic acid
- Adverse effects
- Intravascular thrombosis
- Hypotension
- Must give a 30 min loading dose to prevent hypo
-
Serine protease inhibitors
-
MOA: inhibits fibrinolysis by free plasmin
-
Aprotinin
- serine protease inhibitor
- reduces bleeding from surgery
-
Clotting factors
-
Factor VII deficiency
- fresh-frozen plasma
- prothrombin complex concentrates
- recombinant factor VIIa
-
Hemophilia A
- recombinant factor VIII
- cryoprecipitate
-
Hemophilia B/Christmas disease
- recombinant factor IX products
-
Stuart-Prower defect (X)
- FFP
- prothrombin complex concentrates
-
Von Willebrand disease
- factor VIII concentrates containing VWF
- cryoprecipitate
- Subtopic 6
-
Vitamin K
- MOA: relieves depression of prothrombin activation
-
Use
- Excessive warfarin administration
-
Vitamin K deficiency
- adults
- all neonates
-
Anticoagulation drugs
-
Indirect thrombin inhibitors
-
MOA: Interact with AT III to inhibit thrombin
-
Heparin
- Adverse effects
- BLEEDING
- HIT: Heparin-induced Thrombocytopenia
- Immunogenic, hapten-like response to the factor IV-heparin complex, causing thrombi, thrombocytopenia, and decreased platelet count
- Precautions
- oral causes hematoma - use IV, SC only
- closely monitor: aPTT, protamine concentration, anti-Xa units
- short half-life; use other indirects for more convenient administration
- preferred for pregnant women
- Antidote
- STOP THE DRUG
- protamine sulfate
-
MOA: Inhibit Xa
-
LMWH
- Less side effects, no aPTT monitoring
- EnoxaPARIN
- DaltePARIN
- TinzaPARIN
-
Fondaparinux
- Use in case of HIT
-
Direct thrombin inhibitors
-
MOA: directly bind the active site of thrombin
-
bivalent: irreversible inhibitors also bind to the substrate recognition site
- Bivalirudin
- Hirudin
- recombinant form of hirudin
- Lepirudin
- Good for HIT
- Bad in pts with renal insufficiency
-
Argatroban
-
Use
- USE in HIT
- IV, monitor aPTT
-
Precautions
- Liver clearance
-
Dabigatran
-
Use
- ORAL
- fast onset
-
Precautions
- CONTRAINDICATED in renal failure
- fatal bleeding
- NO ANTIDOTE
-
Vitamin K antagonist
-
Warfarin
-
MOA
- Blocks the γ-carboxylation of the glutamate residue in prothrombin, VII, IX, X, protein C & S by inhibiting VITAMIN K EPOXIDE REDUCTASE
-
Use
- ORAL: 5-10 mg standard dose
- slow onset/offset: 8-12 hrs
- Therapeutic range = INR of 2-3
- 1 week for PT to adjust
-
Adverse reactions
- Skin necrosis (WISN) during first week
- DVT with decreased protein C activity
-
Precautions
- CONTRAINDICATED in pregnancy (crosses the placenta)
- Causes hemorrage, birth defects in the fetus
-
Antidotes
- Excessive anticoagulant effect & bleeding
- STOP THE DRUG
- Give Vit K1, fresh-frozen plasma, prothrombin complex concentrates, rFVIIa
-
Factor Xa inhibitor
-
Rivaroxaban
-
Use
- ORAL
- fast onset
-
Precautions
- LIVER METABOLISM/p450 metabolism
- Subtopic 2
-
Antidote
- Factor Xa
-
ORAL ANTICOAGULANTS
- Drug interactions - oral anticoagulants
-
Direct thrombin inhibitor
- dabigatran
-
Vitamin K antagonist
- warfarin
-
Factor Xa Inhibitor
- rivaroxaban
-
Thrombolytic drugs
-
MOA: binds and activates plasmin
-
Streptokinase
- Hypersensitivity (only use once)
-
Anistreplase
- Complex of human plasminogen + streptokinase
-
MOA: directly converts plasmin to plasminogen
- Urokinase
-
tissue plasminogen activators (t-PAs)
-
MOA: preferentially activates fibrin-bound plasminogen
-
recombinant t-PA
- Alteplase
- Reteplase
-
mutant t-PA
- Tenecteplase
-
Antiplatelet Agents
-
Thromboxane inhibitor
-
MOA: irreversibly inhibits the synthesis of TXA2
- Aspirin
-
ADP receptor antagonists
-
MOA: inhibit the platelet's ADP receptor
-
Clopidogrel
- prodrug
- slow-onset
- Adverse interactions with proton-pump inhibitors (omeprazole)
-
Ticlopidine
- Adverse reactions
- Causes TTP
- GI toxicity, hemorrage, purpura
-
IIb/IIIa receptor antagonists
-
MOA: blocks activation of the IIb/IIIa and vibronectin receptors
- Abciximab
-
MOA: blocks the binding of fibrinogen to the IIb/IIIa receptor only
- Eptfibatide
-
Tirofiban
- smaller molecule